Potent anti-hepatoma efficacy of HCCS1 via dual tumor-targeting gene-virotherapy strategy.
We previously demonstrated that hepatocellular carcinoma suppressor 1 (HCCS1) exerts potent anti-tumor activity. In this study, we constructed a new dual tumor-targeting oncolytic adenovirus vector, PD55-HCCS1, in which E1A was driven by the promoter of progression elevated gene-3, which is hepatoma-specific, and a CMV-HCCS1 expression cassette replaced E1B55. The PD55-HCCS1-mediated selective expression of E1A and HCCS1 in hepatoma cells and tumor-selective cytotoxicity in vitro and in vivo demonstrated the strongest inhibition of BEL-7404 cell xenografts in nude mice among a number of control Ad vectors. These data indicated the efficacy and safety of the PD55-HCCS1 system for HCC treatment.
Zhang
Jian
J
Laboratory for Cellular and Molecular Immunology, Shanghai Cancer Institute, Shanghai, P.R. China.
Gan
Yu
Y
Gu
Jinfa
J
Hu
Jingying
J
Liu
Xinyuan
X
Zhao
Xintai
X
D000256:Adenoviridae / Q000235:genetics; D017500:Adenovirus E1A Proteins / Q000235:genetics; D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000628:therapy*; D045744:Cell Line, Tumor; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000628:therapy*; D051379:Mice; D008819:Mice, Nude; D050130:Oncolytic Virotherapy / Q000379:methods*; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D033921:Vesicular Transport Proteins; D023041:Xenograft Model Antitumor Assays
D017500:Adenovirus E1A Proteins; D000943:Antigens, Differentiation; C489287:Ppp1r15a protein, rat; D011518:Proto-Oncogene Proteins; D025521:Tumor Suppressor Proteins; C503307:VPS53 protein, human; D033921:Vesicular Transport Proteins